Chan Ming-Huan, Lee Chia-Chi, Chen Hwei-Hsien
Institute of Pharmacology and Toxicology Tzu Chi University 701, Section 3, Chung-Yang Road, Hualien 970, Taiwan.
Toxicol Lett. 2006 Jan 25;160(3):179-84. doi: 10.1016/j.toxlet.2005.07.002. Epub 2005 Aug 18.
Toluene is one of the most widely used solvents. Electrophysiological studies indicated that this solvent directly affects various ligand gated ion channels including NMDA, GABA(A), nicotinic and glycine receptors. The effect of toluene on seizures induced by chemoconvulsants acting on these receptors was compared. Mice were pretreated with toluene (100-1000 mg/kg, i.p.) or corn oil followed by a timed intravenous infusion of NMDA, bicuculline, picrotoxin, nicotine or strychnine to induce seizures. Toluene increased seizure thresholds and lethal doses induced by nicotine, NMDA, picrotoxin and bicuculline, but not strychnine in the used doses. The relative susceptibility to anticonvulsant effect of toluene was in the order: nicotine > NMDA > bicuculline > picrotoxin > strychnine. These findings support a unique anticonvulsant profile of toluene and suggest that nicotinic and NMDA receptors may be more sensitive than GABA(A) and glycine receptors to toluene exposure in seizure-related neural circuits.
甲苯是使用最为广泛的溶剂之一。电生理研究表明,这种溶剂会直接影响包括N-甲基-D-天冬氨酸(NMDA)、γ-氨基丁酸A(GABA(A))、烟碱和甘氨酸受体在内的各种配体门控离子通道。比较了甲苯对作用于这些受体的化学惊厥剂所诱发癫痫发作的影响。给小鼠腹腔注射甲苯(100 - 1000毫克/千克)或玉米油进行预处理,然后定时静脉注射NMDA、荷包牡丹碱、印防己毒素、尼古丁或士的宁以诱发癫痫发作。在所使用的剂量下,甲苯提高了由尼古丁、NMDA、印防己毒素和荷包牡丹碱诱发的癫痫阈值和致死剂量,但对士的宁没有影响。甲苯抗惊厥作用的相对敏感性顺序为:尼古丁 > NMDA > 荷包牡丹碱 > 印防己毒素 > 士的宁。这些发现支持了甲苯独特的抗惊厥特性,并表明在癫痫相关神经回路中,烟碱和NMDA受体可能比GABA(A)和甘氨酸受体对甲苯暴露更敏感。